caa a22 4500 445853700 CHVBK 20180317145421.0 cr unu---uuuuu 170323e20110401xx s 000 0 eng 10.1007/s00204-011-0675-4 doi (NATIONALLICENCE)springer-10.1007/s00204-011-0675-4 Nrf2: control of sensitivity to carcinogens [Elektronische Daten] [Stephen Slocum, Thomas Kensler] Induction of enzymes that enhance the detoxication of chemical carcinogens has been a broadly effective strategy for chemoprevention of experimental carcinogenesis in rodent models. Several inducing agents are now in clinical trials to evaluate utility for prevention of cancers associated with unavoidable high exposures to environmental carcinogens. The successes of these pre-clinical and clinical interventions lead to studies to define the molecular basis for protection by these agents, which now include phenolic antioxidants, dithiolethiones, isothiocyanates, and triterpenoids. In the mid-1990s, the NF-E2-related factor 2 (Nrf2) transcription factor was identified as a key regulator of the inducible expression of enzymes such as glutathione S-transferases and NAD(P)H: quinone oxidoreductase in catalyzing the detoxication of reactive electrophiles and oxidants that contribute to the formation of mutations and ultimately cancers. Nrf2 is now recognized to regulate a broad cytoprotective, transcriptional response leading to prevention of damage to DNA, proteins and lipids; recognition, repair and removal of macromolecular damage; and tissue renewal following toxic assaults. Highlighting the importance of this pathway as a determinant of susceptibility to carcinogenesis, multiple studies now demonstrate enhanced incidence, multiplicity, and/or tumor burden in Nrf2-disrupted mice compared to wild-type in models of inflammation and colon cancer, bladder cancer, lung disease and cancer, stomach cancer, mammary cancer, skin cancer, and hepatocarcinogenesis. Springer-Verlag, 2011 Keap1 nationallicence Nrf2 nationallicence Cancer nationallicence Chemoprevention nationallicence Slocum Stephen Department of Biochemistry and Molecular Biology, Johns Hopkins Bloomberg School of Public Health, 21205, Baltimore, MD, USA aut Kensler Thomas Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, 21205, Baltimore, MD, USA aut Archives of Toxicology Springer-Verlag 85/4(2011-04-01), 273-284 0340-5761 85:4<273 2011 85 204 https://doi.org/10.1007/s00204-011-0675-4 text/html Onlinezugriff via DOI 1 review-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s00204-011-0675-4 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Slocum Stephen Department of Biochemistry and Molecular Biology, Johns Hopkins Bloomberg School of Public Health, 21205, Baltimore, MD, USA aut NATIONALLICENCE 700 1- Kensler Thomas Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, 21205, Baltimore, MD, USA aut NATIONALLICENCE 773 0- Archives of Toxicology Springer-Verlag 85/4(2011-04-01), 273-284 0340-5761 85:4<273 2011 85 204 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer